An overview of reverse cholesterol transport

Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver via the plasma compartment. Cellular cholesterol efflux is mediated by HDL, acting in conjunction with the cholesterol esterifying enzyme, lecithin: cholesterol acyltransferase. Cholesteryl ester accumulating in HDL can then follow a number of different fates: uptake in the liver in HDL containing apolipoprotein (particle uptake) by LDL receptors, selective uptake of HDL cholesteryl ester in liver or other tissues involving scavenger receptor B1, or transfer to triglyceride-rich lipoproteins as a result of the activity of cholesteryl ester transfer protein, with subsequent uptake of triglyceride-rich lipoprotein remnants in the liver. Recently, we and others have taken a molecular approach to analysing the different components of reverse cholesterol transport, by over- or under-expression of individual molecules in induced mutant mouse models, or by the study of human mutations involving molecules of reverse cholesterol transport. Such studies reveal that over-expression of the major HDL apoprotein, apolipoprotein A-I, is clearly anti-atherogenic. However, over- or under-expression of molecules such as cholesteryl ester transfer protein, which have opposite effects on HDL levels and reverse cholesterol transport, suggest that both HDL levels as well as the dynamics of cholesterol movement through HDL are involved in the anti-atherogenic actions of HDL.